Mesh implant for use in reconstruction of soft tissue defects

ABSTRACT

The present invention relates to a resorbable polymeric mesh implant, that is intended to be used in the reconstruction of soft tissue defects. The mesh implant comprises at least a first and a second material, wherein the second material is substantially degraded at a later point in time than the first material following the time of implantation. The mesh implant is adapted to have a predetermined modulus of elasticity that gradually is decreased until the mesh implant is completely degraded and subsequently resorbed. Due to the gradual decrease in the modulus of elasticity of the inventive mesh implant, the regenerating tissue may gradually take over the load applied to the tissue defect area.

TECHNICAL FIELD

The present invention relates to a resorbable polymeric mesh implant anda polymeric mesh implant kit. The mesh implant, as well as the kit, isintended to be used in the reconstruction of soft tissue defects. Themesh implant comprises at least a first material and a second material,wherein the second material is substantially degraded at a later pointin time than the first material, following the time of implantation ofthe mesh implant. The mesh implant is adapted to have a substantiallyconstant modulus of elasticity during a short initial time period afterimplantation, after which period the modulus of elasticity is decreaseduntil the mesh implant substantially looses its mechanical propertiesand subsequently is completely degraded and absorbed by the body. Due tothe gradual decrease in the modulus of elasticity of the inventive meshimplant, the regenerating tissue may gradually take over the loadapplied to the tissue defect area until the mesh implant is completelyresorbed. With the inventive mesh implant there is no longer a need forinert, non-resorbable, long term supporting structures.

BACKGROUND ART

Within the field of surgical repair of soft tissue defects, use is oftenmade of a mesh implant made of a non-resorbable material that isinserted to cover the area of the tissue defect. The mesh implant isused in order to support the regenerating tissue, and in, e.g. herniadefects, it works by mechanical closure of the defect and by inducing astrong scar fibrous tissue around the mesh implant. Such a mesh implantis most often made of various plastics, which are known to staybiostable and safe for a number of years after implantation. However,introducing a foreign material into the human or animal body is mostoften accompanied with side effects like migration, chronicinflammation, risk of infection etc. The introduction of a relativelylarge plastic body is also likely to induce a foreign body-reactioncaused by the body's immune defence system. As a result, the meshimplant may crumple up and loose its tissue supporting function.

The above mentioned mesh implants are in particular used in the repairof defects in the abdominal wall, which may be a result from trauma,tumour resection, prolapse or hernia.

A hernia is an abnormal protrusion of a peritoneal-lined sac through themusculoaponeurotic covering of the abdomen, the most common site for ahernia being the groin. Types of hernia are, among others, inguinalhernia or a femoral hernia, hiatal hernia, umbilical hernia andincisional hernia, the latter being a hernia that pushes through a pastsurgical incision or operation.

One suggested theory in the field is that some patients, due to collagenmetabolic disorders, have a genetic predisposition for developingrecurrent hernias. An altered ratio of collagen types I and III in thesepatients, with an increase in collagen type III, is believed to reducethe mechanical strength of connective tissues. The decreased tensilestrength of collagen type III plays a key role in the development ofincisional hernias, see KLINGE, U, et al. Abnormal collagen I to IIIdistribution in the skin of patients with incisional hernia. Eur SurgRes. 2000, vol. 32, no. 1, p. 43-48.

It is in particular in the cases of large or recurrent hernias that thesurgical repair or herniorrhaphy makes use of an inert, non-resorbablemesh implant, as described above. The mesh implant is inserted to coverthe area of the abdominal wall defect without sewing together thesurrounding muscles. This can be done under local or general anesthesiausing a laparoscope or an open incision technique.

Among the laparoscopic techniques used, are the trans-abdominalpre-peritoneal (TAPP) technique and the totally extra-peritoneal (TEP)technique. With the TAPP technique, the pre-peritoneal space is accessedfrom the abdominal cavity, whereupon the mesh implant is placed betweenthe peritoneum and the transversalis fascia. With the TEP technique, themesh implant is again placed in the retroperitoneal space, but the spaceis accessed without violating the abdominal cavity. An open and minimalinvasive technique is the Lichtenstein hernia repair technique, in whichthe upper edge of the mesh implant is attached to the outer side of theinternal oblique and the lower edge of the mesh implant is attached tothe aponeurotic tissue covering the pubis.

Another open minimal invasive technique is the mesh-plug techniquecomprising attaching a mesh implant, as described above in reference tothe Lichtenstein technique, but also inserting a plug pushing theperitoneum in a direction towards the abdominal cavity.

The mesh implant, inserted with any of the above described techniques,is used in order to support the regenerating tissue with minimaltension. It works by mechanical closure of the defect in the abdominalwall and by inducing a strong scar tissue around the mesh implantfibres. The commercially available hernia mesh implants are often madeof various, inert, non-resorbable polymeric materials, typicallypolypropylene, and suffers from the same disadvantages, as describedabove in connection with mesh implants used for reconstruction of softtissue defects in general. However, implantation of large pieces of meshimplants in the abdominal wall cavity, also leads to considerablerestriction thereof. In a study performed by Junge et al, JUNGE, K, etal. Elasticity of the anterior abdominal wall and impact for reparationof incisional hernias using mesh implants. Hernia. 2001, no. 5, p.113-118., the elasticity of the abdominal wall was measured and comparedto that of commercially available non-resorbable hernia mesh implants.It was assumed that the flexibility of the abdominal wall is restrictedby extensive implantation of large mesh implants, the more so if themesh implants are integrated into scar tissue.

In addition, the non-physiological stretching capability of the meshimplants contrast with the highly elastic abdominal wall and can giverise to shearing forces, favouring increased local remodelling and thusrecurrence at the margin. It was concluded that mesh implants used forrepairing inscisional hernia should have an elasticity of at least 25%in vertical stretching and 15% in the horizontal stretching whensubjected to a tensile strength of 16 N/cm, in order to achieve almostphysiological properties.

The progress within hernia repair mesh implant development, as well asin the development of mesh implants for the use of reconstruction ofsoft tissue defects in general, has been towards mesh implants with lessmass in order to minimize foreign body reactions, and larger pore sizes,which on one hand reduce the mass of the mesh implant and on the otherfacilitate ingrowth of tissue.

U.S. Pat. No. 6,319,264 B (TÖRMÄLÄ) 20.11.2001 describes a porous,flexible and fibrous hernia mesh, which is intended to be implantedclose to hernia defects. The mesh comprises two functional layers,wherein the first layer is a rapidly degradable polymer layer facing thefascia, and wherein the second layer is a more slowly degradable polymerlayer. The first polymer layer has a fast resorption profile,approximately 14 days, said first layer promotes scar tissue formationdue to inflammatory reactions induced by the polymer degradation and dueto the porous structure of the first layer.

The second polymer layer has a longer resorption time, approximately 6months, and thus supports the area until the scar tissue is strongenough to resist pressure and prevent recurrent hernia formation. Anoptional third dense, thin, bioabsorbable layer is described, whichprevents agents that could cause tissue to tissue adhesion from movingfrom the hernia area through the mesh and onto the surrounding tissueduring the first weeks after the operation. The mesh described in U.S.Pat. No. 6,319,264 acts as a temporary support until connective scartissue has strengthened enough and can replace the mesh, when the secondlayer finally degrades.

However, U.S. Pat. No. 6,319,264 is silent as to the load situationfound over the tissue defect area and to the modulus of elasticity ofthe hernia mesh. In the above described mesh, only the second layer isdesigned to support the tissue during the regenerative phase. The meshmaterial is by the body regarded as an inert material, in that no majorchanges in mechanical properties are observed until degradation hasreached to such a point where the material starts to crack with a moreor less catastrophic change in mechanical properties taking place.

The complex but well orchestrated sequence in wound healing starts withhemostasis and the wound is usually fully closed within 10 to 14 days.However, depending on the individual and the size of the wound, thehealing sequence may be faster or slower. This is especially true if thewound is infected. Collagen remodelling and deposition is however acontinuous process slowly building up the strength in the woundedtissue. Fibroblasts play a key role in the early phase of thewound-healing and are present already from day 2 or 3. The key role ofthe fibroblasts is to deposit new collagen into the wounded arearebuilding the extra-cellular matrix and thus repairing the woundedtissue. This first deposited collagen is most often laid down in arandom non-oriented fashion and is often referred to as scar tissue.However, by stimulating the wound already during the early or acutephase of wound healing we have reason to believe that a denser andstronger collagen layer is deposited. These findings implicate that thesurgical mesh used for soft tissue reconstruction should possessproperties that would allow the mesh to become more compliant with thesurrounding tissue during the early phase of wound healing and acontinuous increase in compliance could be visualized after theremodelling phase starts. After the acute wound-healing phase is over,the wound is often remodelled, i.e. the first deposited collagen isreplaced by a more structurally rigid collagen. During this remodellingperiod, the newly formed tissue will undergo several phases, duringwhich the tissue gradually becomes more specific to support the variousstress situations found in the area. Following the teachings of Junge etal, a mesh implant used for reconstruction of soft tissue defects,should have an elasticity that is compatible with the elasticity of thesurrounding tissue, so that the flexibility of said tissue is notsubstantially restricted.

It is therefore believed that device compliance will play a key role inthe remodelling sequence of the first deposited collagen. But to oursurprise we have also found that meshes used for soft tissue repair andwhich alter their mechanical properties in the very early phase of thewound healing sequence rather than in the remodelling phase of thewound, may stimulate gross infiltration of collagen into the knittedmesh construct. This early infiltration of collagen may play a crucialrole in the strength of the wound at a later stage. It appears that apolymeric mesh for reconstruction of soft tissue defects should be sodesigned that it will allow for early stimulation of the newly depositedtissue. This can be accomplished by allowing an early change in themodulus of the implant so that it gradually become more and morecompliant to the surrounding tissue.

The inventors of the present invention therefore suggest that a deviceused to temporarily support the tissue defect in the area where thetissue is exposed to various stress situations should be so designed asto allow for an early change in the modulus of the implant, bestexpressed as an increased elongation, thus allowing an early stimulationof the deposited collagen in the wound area followed by a gradual changein compliance of the implant allowing the newly formed tissue togradually take over the load during the remodelling phase and thus buildup the strength and compliance needed to take over the full load oncethe support from the temporarily implanted device is lost.

DISCLOSURE OF THE INVENTION

The object of the present invention is therefore to provide a resorbablemesh implant for use in reconstruction of soft tissue defects, themechanical properties of which stimulates the ingrowing, regeneratingtissue, and at the meantime allowing the regenerated tissue to graduallytake over the load found in the tissue defect area until the meshimplant substantially looses it mechanical properties and subsequentlyis completely resorbed. Another object of the present invention is toprovide a polymeric mesh implant kit.

These objects are achieved by the present invention according to thepreambles of the independent claims and provided with the featuresaccording to the characterizing portions of the independent claims.Preferred embodiments of the present invention are set forth in thedependent claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 schematically shows an embodiment of the present invention,wherein the mesh implant comprises two materials A and B,

FIG. 2 schematically shows an alternative embodiment of the presentinvention, wherein the mesh implant comprises three materials A-C,

FIG. 3 schematically shows a cross section of one structural design ofthe embodiment shown in FIG. 3,

FIG. 4 shows the modulus of elasticity of the mesh implant shown in FIG.1 as a function of time (not to scale),

FIG. 5 shows the modulus of elasticity of the mesh implant shown inFIGS. 2 and 3 as a function of time (not to scale).

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

An embodiment of the present invention is shown in FIG. 1, wherein themesh implant comprises two resorbable polymeric materials, material Aand material B. Material A is characterized by a time of substantialdegradation, t_(A), and a modulus of elasticity, E_(A). Consequently,material B is characterized by a time of substantial degradation, t_(B),and a modulus of elasticity, E_(B). Material B is substantially degradedat a later point in time, following the time of implantation of the meshimplant, than material A, i.e. t_(A)<t_(B). The time of substantialdegradation herein being defined as the point in time at which thematerial substantially change its mechanical properties. One could alsodefine the time of substantial degradation as the point in time at whichthe mechanical integrity of the material no longer provide the meshimplant with mechanical properties that contribute to the object of theinventive mesh implant. For instance, the mechanical properties of thematerial may have declined at the time of substantial degradation, sothat the mechanical strength of the material is less than approximately30% of its initial strength.

The modulus of elasticity of material A is higher than the modulus ofelasticity of material B, i.e. E_(A)>E_(B), and consequently, theelongation of material A is lower than the elongation of material B. Itis here understood that E_(A) and E_(B) is the modulus of elasticity ofthe respective material in the present configuration. Thus, a material Awill, for example, generally have a lower E_(A) if the material A isdesigned as having a perforated structure than if the same material Aexhibits a homogenous structure. For the different materials of theinventive mesh implant, a modulus of elasticity is preferably within therange of 300 kPa-3 GPa. It is to be noted that the modulus of elasticityof a material need not to have the same value in all directions, thusthe modulus of elasticity in for instance the vertical direction neednot to be identical with the modulus of elasticity in the horizontaldirection. The burst strength method as described in ASTM D 3787-1 isespecially useful in characterizing mesh structures. Since modulus ofelasticity can be difficult or impossible to elucidate the compliance ofthe implant can more preferably be given as the elongation, recalculatedfrom the distension, at certain load values using the burst test methodabove.

t_(A) is in the time range of 2 to 13 days or more preferably 3 to 9days after the time of implantation, i.e. t=t₀, and t_(B) is at least3-18 months after the time of implantation, preferably in the time rangeof 6-12 months.

In the mesh implant according to the embodiment described above,material A and material B can be structurally designed as two separateperforated layers, respectively, arranged on top of each other. Also,material A and material B can be partly or fully incorporated with eachother, which will be explained in further detail below. Afterimplantation the mesh implant can be fixed with for instance suitablesutures, staples, fixation, pins, adhesives or the like. In someapplications of the implant, the pressure from the surrounding tissuemay be enough for initial fixation until newly regenerating tissueanchors the implant by tissue through growth.

Material A acts as an initial and temporary support during the primarywound healing time period t=t₀−t_(A), during which E_(A) is high andsubstantially constant, allowing the elongation of the mesh implant tobe no more than in the range of 0 to 20%, but more preferably in therange of 0-10%.

Material A is substantially degraded at time t_(A), leaving material Bto alone carry the load applied to the tissue defect area. However, dueto the significantly lower modulus of elasticity of material B, part ofthe load will be transferred onto the surrounding and ingrowing tissue.The mechanical stimulation of the wound area will thus stimulate thecells to deposite new extracellular matrix as well as stimulateremodelling of the existing tissue to be oriented according to theexisting load pattern and gradually take over the load carried by themesh implant during the time period of t_(A)−t_(B). Thus, material Bfacilitates the mechanical stimulation of the surrounding tissue, e.g.aponeurotic structures, to develop the strength needed to finally takeover the total load applied to the tissue defect area when the meshimplant is substantially degraded and subsequently completely resorbed.

FIG. 4 shows the modulus of elasticity, E, of the mesh implant shown inFIG. 1 comprising material A and material B, as a function of time, t.During t=t₀−t_(A), material A practically carries the entire load overthe tissue defect area due to the higher modulus of elasticity of saidmaterial. E is substantially constant with respect to time and thuscorresponds to E_(A) during said time period. As described above, E isduring the time period of t=t₀−t_(A) high enough not to allow anysubstantial elongation of the mesh implant. A more or less suddenincrease in elongation is observed around t=t_(A) when the mechanicalproperties of material A starts to change as a consequence of theongoing degradation. During t=t_(A)−t_(B), E=E_(B) since the load overthe tissue defect area is carried by material B alone, as describedabove. Preferably, E_(B) corresponds to an elongation of the meshimplant that is compatible with the elasticity of the surroundingtissue, so that the flexibility of said tissue is not substantiallyrestricted.

In an alternative embodiment of the inventive mesh implant, the meshimplant comprises a third resorbable polymeric material C, characterisedby t_(C) and E_(C) with t_(A)<t_(B)<t_(C), and E_(A)>E_(B)>E_(C). Alsohere it is understood that E_(C) is the modulus of elasticity ofmaterial C in its present configuration, as explained above. Thus, themesh implant comprises in the alternative embodiment three materials A,B and C. In said alternative embodiment the materials A through C can bestructurally designed as three separate perforated layers, arranged ontop of each other, as seen in FIG. 3. The materials A through C can alsobe partly or fully incorporated with each other, as explained in furtherdetail below. Two of the materials can be partly or fully incorporatedwith each other, but not the third, wherein any combination of materialsmay be possible.

When the mesh implant according to the alternative embodiment isinserted into the body (see discussion above that refers to implantationof the mesh implant according to the embodiment comprising material Aand B) material A, due to its high modulus of elasticity, acts as aninitial and temporary support during the primary wound healing timeperiod t=t₀−t_(A). Material A is substantially degraded at time t_(A),at which time material A substantially looses its mechanical properties,as described above. Material B, due to its higher modulus of elasticitythan material C, then carries the load applied to the tissue defectarea, but due to the lower modulus of elasticity of material B than ofmaterial A, part of the load will be transferred onto the surroundingand ingrowing tissue. At time t_(B) material B is substantiallydegraded, leaving material C to carry the load applied to the softtissue defect area. Due to the even lower modulus of elasticity ofmaterial C, further load will be transferred to the surrounding tissue.As described above, material B and material C thus allow a biomechanicalstimulation on the tissue, that will enable it to regenerate and remodelinto a load bearing tissue, e.g. aponeurotic structures, tendons orligaments, that gradually will take over the load carried by the meshimplant during the time period of t_(A)−t_(C).

E as a function of time for the alternative embodiment shown in FIGS. 2and 3, is shown graphically in FIG. 5. t_(A) is, as in the embodimentshown in FIG. 1, approximately 2 to 13 days or more preferably 3 to 9days, and t_(C) is at least 3-18 months after the time of implantation,preferably in the time range of 6-12 months. t_(B) can thus be anywherebetween 14 days and 18 months, as long as t_(A)<t_(B)<t_(C). In saidalternative embodiment, material C acts as the last substantiallydegraded material of the mesh implant and E_(C) preferably correspondsto an elongation of the mesh implant that is compatible to theelasticity of the surrounding tissue, so that the flexibility of saidtissue is not substantially restricted. Thus, E_(B) can have apredetermined value anywhere between E_(A) and E_(C).

The mesh implant according to the present invention, thus strives toimitate the ideal E versus t situation, shown as a dotted line in FIGS.4 and 5, of a resorbable mesh implant used to temporarily support softtissue defects during reconstruction thereof. In the ideal situation, Eof the mesh implant is during the primary wound healing time periodsubstantially constant and high enough not to allow any substantialelongation of the mesh implant, whereupon the mesh implant is degradedwith a gradual decrease in E so that the newly formed tissue maygradually take over the load applied to the tissue defect area duringthe remodelling phase. In the ideal situation, the mesh implant thusbiomechanically stimulates the surrounding tissue to build up thestrength and compliance needed to take over the full load once thesupport from the temporarily implanted device is lost after at least3-18 months. During the final stage of the remodelling phase, themodulus of elasticity of the mesh implant preferably corresponds to anelongation of the mesh implant that is compatible with the elasticity ofthe surrounding tissue, so that the flexibility of said tissue is notsubstantially restricted. The modulus of elasticity of various softtissues varies over a broad range from tendons having elastic modulusaround 700 MPa to very low modulus found in elastine rich tissue wheremodulus can be around 300 kPa. The modulus above is only approximatevalues due to the often non-linear behaviour of soft tissue. If theinventive mesh implant is intended to be used in the reconstruction ofdefects in the abdominal wall, following the teachings of Junge et al,the elasticity of the mesh implant, during the final stage of theremodelling phase, preferably corresponds to an elongation of 18-32%when subjected to a load of 16 N/cm.

Since a high modulus of elasticity of the mesh implant corresponds to alow elongation thereof, the ideal situation can just as well bedescribed by ways of elongation of the mesh implant as a function oftime. In that case the mesh implant is preferred to have a very low andsubstantially constant elongation during the first days of the woundhealing period followed by a gradual increase in elongation. During thefinal stage of the remodelling phase, the mesh implant preferably has anelongation as described above.

The inventive mesh implant can thus comprise any number of materials, aslong as it strives to imitate the ideal E versus t situation. However,due to manufacturing reasons, the number of materials is preferably notmore than five and more preferred 3-4.

In yet an alternative embodiment of the inventive mesh, the mesh implantaccording to any of the above described embodiments, can comprise afurther resorbable polymeric material D (not shown), which hasessentially the same characteristics as material A, with respect to timeof substantial degradation, t_(D). Material D can, in fact, be the samematerial as material A, but present in another configuration such thatE_(D) is not equal to E_(A). Material D is adapted to provide an extrasupportive structure during t=t₀−t_(A) and enables more ingrowth offibrous tissue. Material D can be structurally designed as a separateperforated layer or can be partly or fully incorporated with any of theother materials of the mesh implant, see further discussion below.

The mesh implant can also be provided with still a further material E(not shown), which material E is substantially degraded approximately atthe same point in time as any of the other materials present in the meshimplant, and thus in fact be the same material as any of the other saidmaterials. Material E can be present in another configuration than thatof the material with which it has approximately the same time ofsubstantial degradation, so that E_(E) is not equal to the modulus ofelasticity of that material, or material E can have approximately thesame modulus of elasticity as that material. Material E can bestructurally designed as a separate perforated layer or can be partly orfully incorporated with any of the other materials of the mesh implant,see further discussion below.

Optionally a thin resorbable film (not shown) can be applied to the meshimplant, in any of the above described embodiments, in order to preventadhesion of the mesh implant to surrounding tissues. If the mesh implantis intended to be used in the repair of abdominal wall defects, the thinfilm is preferably applied on the surface of the mesh implant facingtowards the abdominal cavity in order to in particular prevent adhesiononto the intestines. Said film is preferably a thin hydrophilic film,for instance a carbohydrate film, with a thickness in the range of 1-300microns, that forms a hydrogel structure when the film is brought intocontact with fluids contained in the tissue.

The inventive mesh implant preferably has mechanical properties thatenables it to be inserted into the body with any conventionally usedtechnique for implantation of mesh implants used for reconstruction ofsoft tissue defects, for instance any of the techniques described inreference to the implantation of hernia mesh implants. A mesh implant isherein being defined as an implant device with any type of through goingperforation, including pores, naturally occurring perforations orartificially created perforations, which extend from the proximalsurface to the distal surface of the implant device, so that there is acommunication between said proximal and distal surface. The materials ofthe inventive mesh implant, can be fibres made from any bioresorbablepolymer, copolymer, polymer blend or polymer composite, or can becombined assorted bioresorbable polymer parts, as long as the materialshave suitable predetermined times of substantial degradation and modulusof elasticity, so that when the materials are combined, the inventivemesh implant strives to imitate the ideal E versus t situation of aresorbable mesh implant used to temporarily support soft tissue defectsduring reconstruction, as described above.

Non-limiting examples of such synthetic resorbable materials are variouscombinations of the monomers glycolide, lactide and all stereoismerstherof, trimethylene carbonate, epsilon-caprolactone, dioxanone ordioxepanone. Depending on the desired mechanical properties and thechoice of manufacturing method, several of the homopolymers orcopolymers containing two or more of the above-mentioned monomers can beused to manufacture the mesh structure. Yet other examples of syntheticresorbable polymers that can be utilized are various aliphaticpolyurethanes, such as polyureaurethanes, polyesterurethanes andpolycarbonateurethanes, and also materials such as polyphosphazenes orpolyorthoesters.

The materials of the inventive mesh implant can have a woven or knittedstructure with pores of a suitable pore size, or can have a non-woven,for instance electro-spun, structure, wherein the (electro-spun)non-woven structure can further be furnished with man made through andthrough holes. When two or more materials are incorporated with eachother, fibres of said materials, respectively, can be jointly woven,knitted or non-woven into the same suitable structure. Also variousmaterials can be spun into fibres which are braided, twisted into amultifilament produced from two or more materials, which multifilamentis woven, knitted or non-woven into said suitable structure. It isunderstood that any combination of fibers in the form of monofilament,filament bundles, multifilament or braided or twisted multifilament canbe combined into the desired structure. Moreover anyone of thefiberstructures mentioned above may be individually coated as well asthe final product. Preferably however, material A, and D, has, or isincorporated into, a porous, woven or knitted structure with a pore sizepreferably in the range of 50-4000 microns, or a non-woven, for instanceelectro-spun structure, since a porous structure with a pore size in theabove mentioned range, or a non-woven structure, enable for fibroblastsand other connective tissue cells to grow into the pores, or into thenon-woven structure, during the primary wound healing period. However,material A and D, need not to have, or be incorporated into, the samestructural design, thus material A can have, or be incorporated into, awoven or knitted structure while material D has, or is incorporatedinto, a non-woven structure and vice versa.

The last substantially degraded material of the inventive mesh implant,preferably has, or is incorporated into, a porous woven or knittedstructure, with a pore size preferably in the range of 0.5-4 mm, morepreferred 1-3 mm, in order to minimize the mass of the mesh implant aswell as maximizing the tissue supporting effect of said lastsubstantially degraded material.

Any other material can have, or be incorporated into, either a porouswoven or knitted structure, or a non-woven, for instance electro-spunstructure. If said materials have, or are incorporated into, a porouswoven or knitted structure it is preferred, however not mandatory, thatalso this structure has a pore size in the range of 0.5-4 mm, morepreferred 1-3 mm for reasons as described above.

The mesh implant can also be provided with trough going macro-pores,that extend from the proximal surface to the distal surface of the meshimplant, in order to further facilitate the communication between theproximal and distal surfaces of the mesh implant.

Shown schematically in FIG. 3, is a cross section of a possiblestructural design of the inventive mesh implant comprising materials A,B and C, wherein material A has a non-woven structure on top of materialB and C, which are incorporated with each other into a woven or knitted,porous structure. However, it is pointed out that the structural designshown in FIG. 3, is not preferred to the other possible structuraldesigns of the inventive mesh implant.

The area weight of the inventive mesh as described above is preferably20 to 300 g/m2 or more preferably 30 to 150 g/m2 in its dry state.

The inventive mesh can further comprise bioactive or therapeuticsubstances naturally present in humans or of foreign origin. Thesesubstances include, but are not limited to, proteins, polypeptides,peptides, nucleic acids, carbohydrates, lipids or any combinationsthereof. Especially considered are growth factors, such as PDGF, TGF orFGF, or components of the naturally occurring extracellular matrix,including cytokines, fibronectins, collagens, and proteoglycans such asbut not limited to hyaluronic acid. Therapeutic substances that areconsidered include, but are not limited to, antibiotic drugs and painrelieving substances. Bioactive or therapeutic substances of human orforeign origin can be entrapped within the porous structure of theimplant or incorporated through covalent or other chemical or physicalbonding, in an active state or as precursors to be activated upon anyphysical or chemical stimuli or modification.

The present invention also refers to a polymeric mesh implant kit. Thekit comprises at least a first and a second material, wherein themodulus of elasticity of the second material is lower than the modulusof elasticity of the first material and wherein the second material issubstantially degraded at a later point in time than the first material,however any number of the above mentioned materials can be present inthe kit. The materials are provided in the kit as separate structurallydesigned layers and/or as materials fully or partly incorporated witheach other, wherein any combination of materials is possible, by meansof any of the above described ways. Each material has a predeterminedmodulus of elasticity in its present configuration, as defined above,and a predetermined time of substantial degradation, as defined above.Thus, the user of the kit can combine any number of materials into apolymeric mesh implant, as defined above and that strives to imitate theideal E versus t situation described above with reference to FIGS. 4 and5, that is tailored for each individual patient and for said patientsspecific needs, depending on the nature of the soft tissue defect to berepaired. At least one of the materials preferably has a time ofsubstantial degradation within the time range of 2 to 13 or morepreferably 3 to 9 days, and preferably has a predetermined modulus ofelasticity that does not allow an elongation of the mesh implant, oncecombined, to be no more than in the range of 0-20%, preferably no morethan in the range of 0-10%. At least one of the materials preferably hasa time of substantial degradation within the time range of 3-18 months,preferably 6-12 months, and preferably has a modulus of elasticity thatcorresponds to an elongation of the mesh implant, once combined, that iscompatible with the elasticity of the surrounding tissue, so that theflexibility of said tissue is not substantially restricted. As describedabove, the materials can have a porous, woven or knitted, or anon-woven, for instance electro-spun structure, wherein the(electro-spun) non-woven structure can further be furnished with manmade through and through holes. At least one of the materials, or atleast one combination of materials, can be provided with a thinresorbable film, preferably a thin hydrophilic film as described above,in order to prevent adhesion of the mesh implant, once combined, ontosurrounding tissue. Said film can also be provided in the kit as aseparate item and be combined with the selected materials, so that themesh implant, once combined, is provided with said film for the abovementioned reason. Preferably, at least one of the materials of the kitthat have a time of substantial degradation within the time range of 2to 13 days or more preferably 3 to 9 days, has a porous structure with apore size in the range of 50-4000 microns or has a non-woven, forinstance electro-spun structure, for reasons as described above.Preferably at least one of the materials of the kit that have a time ofsubstantial degradation within the time range of 3-18 months, has aporous structure with a pore size in the range of 0.5-4 mm microns, morepreferred 1-3 mm, for reasons as described above. Further, at least oneof the materials, or at least one combination of materials, of the kitcan comprise bioactive or therapeutic substances naturally present inhumans or of foreign origin, as described above.

However, it is understood that the skilled person is capable of choosingsuitable materials, as defined above, in order to construe a polymericmesh implant that is tailored for each individual patient and for saidpatients specific needs, depending on the nature of the soft tissuedefect to be repaired, without having at hand the inventive kit.Therefore, the present invention also encompass the tailoring of aspecific polymeric mesh implant for the specific soft tissue defect tobe reconstructed, by choosing and combining suitable materials.

It will be understood that the invention is not restricted to the abovedescribed exemplifying embodiments thereof and that severalmodifications are conceivable within the scope of the following claims.

EXAMPLE 1

Two knitted mesh structures, both composed of different co-knittedresorbable mono-multifilament constructions, was implanted into theabdominal wall of 12 Sprague-Dawley rats together with two commerciallyavailable meshes, polypropylene and polyethylene terephthalate,indicated for hernia repair. The resorbable knitted meshes were madefrom 50/50% and 35/65% glycolide/ε-caprolactone monofilaments andlactide/e-caprolactone/trimethylene-carbonate multifilamentsrespectively. The area weight of the meshes was 125 g/m2 respective 168g/m2 and the max burst load was measured to 206 N respective 224 Naccording to ASTM D 3787-1. Elongation, measured at 16 N/cm, was 5% forboth meshes. The mesh was subjected to in vitro degradation in aphosphate buffer solution at 37° C. to study the effect of the fastdegrading monofilament material made from glycolide/ε-caprolactone onthe overall mechanical properties of the mesh construct. After 6 days,about 50% of the strength was lost in the fast degrading monofilamentand after 7 to 8 days little or no contribution to the overall mechanicsof the mesh comes from the fast degrading glycolide/e-caprolactonemonofilament. The mechanics was fully taken over by the slower degradinglactide/e-caprolactone/trimethylene-carbonate multifilament resulting ina max burst strength in the range 175 to 220 N after 10 and up to 28days with a slight difference between the two meshes. The elongation at16 N/cm was measured to 5 to 7% in the time span 0 to 6 days andthereafter started to increase to 15 respective 25% after 15 days andthereafter a slight decrease to 14 respective 22% after 28 days.

In comparison, the polypropylene and polyethylene terephthalate meshrespectively showed a max burst load of about 180 N for both meshes andan elongation at 16 N/cm of 7% respective 12%. These values are constantover the time period 0 to 28 days.

Implantation was performed with EtO sterilized samples of bothresorbable and inert polypropylene mesh. The rectus abdominis musclesheath was opened and the muscle was moved laterally. The mesh structurewas inserted outside the peritoneum without injuring the peritonealmembrane. The rectus abdominus muscle was slipped back to cover theimplant and a suture was placed in the muscle sheath to secure theposition of the implant. The animals was euthanized after 6 weeks andthe implant with surrounding tissue were removed and fixated in bufferedformaldehyde before histology specimens were prepared and stained withvan Gieson stain.

For both the polypropylene and polyethylene terephthalate controls atypical foreign body response was observed around each of the fiberswith very little or no collagen infiltration.

For the resorbable mesh, the fast degrading fibers originating from theglycolide/ε-caprolactone were substantially degraded, in agreement withthe in-vitro observation above, but with less expressed inflammatoryreaction relative the polypropylene mesh. The most remarkable finding isthe fine network of collagen between the multifilament bundles. Thedeposition and infiltration of collagen is thought to origin from theincreased mechanical stimulation of the tissue when the polymeric meshgradually looses its strength. Stimulation from early release ofdegradation products from the fiber may also be a contributing factorfor the integration of collagen into the multifilament fiber bundles.

1. A resorbable polymeric mesh implant whose implant configurationvaries over time after implantation for use in reconstruction of softtissue, wherein the resorbable polymeric mesh implant comprises: atleast a first material and a second material, wherein the secondmaterial is substantially degraded at a later point in time than thefirst material, wherein the modulus of elasticity of the mesh implant isinitially substantially constant following a time of implantation anduntil said first material is substantially degraded, wherein the modulusof elasticity of the mesh implant substantially decreases after thefirst material is substantially degraded.
 2. A resorbable polymeric meshimplant according to claim 1, wherein the mesh implant is configured foruse in reconstruction of soft tissue defects.
 3. A resorbable polymericmesh implant according to claim 1, wherein the first substantiallydegraded material is substantially degraded at a point in time within atime range of 2-13 days following implantation.
 4. A resorbablepolymeric mesh implant according to claim 1, wherein the modulus ofelasticity of the mesh implant is such that, before the first materialis substantially degraded, an elongation of the mesh implant is in arange of 0 to 20% when subjected to a load of 16 N/cm.
 5. A resorbablepolymeric mesh implant according to claim 4, wherein the elongation ofthe mesh implant is in a range of 18 to 32%, when subjected to a load of16 N/cm, after the first material has substantially degraded.
 6. Aresorbable polymeric mesh implant according to claim 1, wherein the meshimplant further comprises a third material that is substantiallydegraded at a later point in time than the second material, wherein themodulus of elasticity of the mesh implant is substantially equal to amodulus of elasticity of the third material in the implant configurationafter the second material is substantially degraded.
 7. A resorbablepolymeric mesh implant according to claim 1, wherein the lastsubstantially degraded material has a modulus of elasticity in theimplant configuration that is compatible with the elasticity ofsurrounding tissue so that a flexibility of said tissue is notsubstantially restricted.
 8. A resorbable polymeric mesh implantaccording to claim 1, wherein a last substantially degraded material issubstantially degraded at a point in time within a time range of 3-18months following implantation.
 9. A resorbable polymeric mesh implantaccording to claim 1, wherein materials are chosen in order to constructa mesh implant that is tailored for a specific soft tissue to bereconstructed.
 10. A resorbable polymeric mesh implant according toclaim 1, wherein the mesh implant is provided with a resorbable film inorder to prevent adhesion of the mesh implant to surrounding tissue. 11.A resorbable polymeric mesh implant according to claim 10, wherein theresorbable film is a hydrophilic carbohydrate film.
 12. A resorbablepolymeric mesh implant according to claim 1, wherein the first materialand/or the second material has a porous structure with a pore size inthe range of 50-4000 microns.
 13. A resorbable polymeric mesh implantaccording to claim 1, wherein the first material and/or the secondmaterial has or is incorporated into a non-woven structure.
 14. Aresorbable polymeric mesh implant according to claim 1, wherein the lastsubstantially degraded material has a pore size in the range of 0.5-4mm.
 15. A resorbable polymeric mesh implant according to claim 1,wherein the modulus of elasticity of the mesh implant is such that,before the first material is substantially degraded, the elongation ofthe mesh implant is in a range of 0 to 10%.